Liu et al.

Trials (2020) 21:622

https://doi.org/10.1186/s13063-020-04478-w

STUDY PROTOCOL Open Access

Efficacy of chloroquine versus lopinavir/

ritonavir in mild/general COVID-19
infection: a prospective, open-label,
multicenter, randomized controlled clinical
study
Xi Liu1†, Huili Chen1†, Yuqi Shang1†, Hongqiong Zhu1, Gongqi Chen1, Yuanli Chen2, Shaoxuan Liu3,
Yaoyong Zhou1, Mingxing Huang1*, Zhongsi Hong1* and Jinyu Xia1*

Abstract
Background: The outbreak of COVID-19 (caused by SARS-Cov-2) is very serious, and no effective antiviral treatment
has yet been confirmed. The adage “old drug, new trick” in this context may suggest the important therapeutic
potential of existing drugs. We found that the lopinavir/ritonavir treatment recommended in the fifth edition of the
Treatment Plan of China can only help to improve a minority of throat-swab nucleic-acid results (3/15) in hospitals.
Our previous use of chloroquine to treat patients with COVID-19 infection showed an improvement in more throat-
swab nucleic-acid results (5/10) than the use of lopinavir/ritonavir.
Methods/design: This is a prospective, open-label, randomized controlled, multicenter clinical study. The study
consists of three phases: a screening period, a treatment period of no more than 10 days, and a follow-up period
for each participant. Participants with COVID-19 infection who are eligible for selection for the study will be
randomly allocated to the trial group or the control group. The control group will be given lopinavir/ritonavir
treatment for no more than 10 days. The trial group will be given chloroquine phosphate treatment for no more
than 10 days. The primary outcome is the clinical recovery time at no more than 28 days after the completion of
therapy and follow-up. The secondary outcomes include the rate of treatment success after the completion of
therapy and follow-up, the time of treatment success after no more than 28 days, the rate of serious adverse events
during the completion of therapy and follow-up, and the time to return to normal temperature (calculated from
the onset of illness) during the completion of therapy and follow-up. Comparisons will be performed using two-
sided tests with a statistical significance level of 5%.
(Continued on next page)

* Correspondence: huangmx5@mail.sysu.edu.cn; hongzhs@sysu.edu.cn;

xiajinyu@mail.sysu.edu.cn
†
Xi Liu, Huili Chen and Yuqi Shang contributed equally to this work.
1
Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen
University, Zhuhai, China
Full list of author information is available at the end of the article

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Liu et al. Trials (2020) 21:622 Page 2 of 9

(Continued from previous page)

Discussion: This experiment should reveal the efficacy and safety of using chloroquine versus lopinavir/ritonavir for
patients with mild/general COVID-19 infection. If the new treatment including chloroquine shows a higher rate of
throat-swab SARS-CoV-2 real-time fluorescent reverse transcription polymerase chain reaction (RT-PCR) negativity
and is safe, it could be tested as a future COVID-19 treatment.
Trial registration: Chinese Clinical Trial Registry, ID: ChiCTR2000029741. Registered on 11 February 2020.
Keywords: COVID-19, Chloroquine, Lopinavir/ritonavir, Randomized controlled clinical study, Efficacy

Introduction Multiple studies have found that chloroquine has anti-

Background
In December 2019, patients with unexplained pneumonia
appeared in Wuhan, China, and were subsequently identified
as a having a novel type of coronavirus. On 30 January 2020,
the World Health Organization named it “COVID-19 (Cor-
ona Virus Disease-2019, caused by Severe Acute Respiratory
Syndrome Corona Virus (SARS-Cov-2)).” The COVID-19
epidemic is now spreading throughout the world.
Coronavirus is a single-stranded, positive-strand RNA
(ribonucleic acid) virus with an envelope [1]. There are
currently no clinically specific drugs for HCoVs (Human
Corona Viruses). Recently, the National Health Commis-
sion of China announced a new coronavirus-infection-
related pneumonia diagnosis and treatment program (the
fifth edition, URL: http://www.nhc.gov.cn/yzygj/s7653p/2
02002/3b09b894ac9b4204a79db5b8912d4440/files/72603
01a393845fc87fcf6dd52965ecb.pdf), which proposed the
trial of lopinavir/ritonavir for its antivirus effect [2–4].
Our previous use of this drug combination found that the
effect of lopinavir/ritonavir on COVID-19 was unsatisfac-
tory, as it only helps to improve the minority of throat-
swab nucleic-acid results (3/15).
Chloroquine is not only used as an antimalarial drug,
but is also used for the treatment of autoimmune diseases
due to its immunomodulatory activity [5].
Previous studies have shown that chloroquine exerts
antiviral effects through the following mechanisms:
SARS-CoV activity:
1. Chloroquine can inhibit viral replication by
reducing the terminal glycosylation of the
angiotensin-converting enzyme 2 (ACE2)
receptor on Vero E6 cells and interfering
with the binding of SARS-CoV to the ACE2
receptor [13, 14]
2. Chloroquine inhibits the replication of HCoV-
229E (and SARS-CoV, both belong to the α-
group HCoVs) by inhibiting the activation of
p38 mitogen-activated protein kinase (MAPK)
in the L132 human embryonic-lung-cell
line [15]
3. The spike protein (S protein) of SARS-CoV-2 is
similar in structure to that of SARS-CoV, and can
bind to the ACE2 receptor on the host-cell surface
to infect the host epithelial cells [16]
4. Remdesivir (GS-5734) and chloroquine (Sigma-
C6628) can effectively inhibit SARS-CoV-2 infec-
tion [17]
This study will compare the efficacy, safety, and im-
pact on patient compliance between the chloroquine
phosphate regimen with the lopinavir/ritonavir regimen
in mild/general COVID-19 infection.

1. It can change the pH of acidic organelles [6] (such Methods/design

as endosomes), so inhibits infections such as Borna
disease virus [7], avian leukemia virus [8], and Zika
virus [9]
2. It can change the glycosylation pattern of the HIV
virus gp120 envelope, which inhibits the replication
of HIV (human immunodeficiency virus) virus in
CD4 + T cells [10]
3. It can effectively inhibit autophagy in the lungs of
avian influenza H5N1 mice and reduce the damage
to the alveolar epithelium [11]
4. It inhibits viral replication by blocking the
autophagy phenomenon induced by the Zika virus,
and can cut off vertical infection of the Zika virus
from the maternal-fetal pathway [12]
Setting
This randomized controlled trial is to be conducted at the
Fifth Affiliated Hospital of Sun Yat-sen University, the
Ninth People’s Hospital of Dongguan, Zhongshan Second
People’s Hospital, and Jiangmen Central Hospital.
These hospitals are located in Guangdong, China. The
clinical research flowchart (CRF) of the research process
is shown in Fig. 1.
Once the volunteered participants have been included,
researchers will explain the research procedures in detail
and require them to sign a written informed consent
form which is signed by the subjects or their legal repre-
sentative. All participants can withdraw their consent at
any time during the trial.
Liu et al. Trials (2020) 21:622
Fig. 1 The clinical research flowchart
Design
This is a prospective, open-label, randomized con-
trolled, multicenter clinical study with two arms. Eli-
gible patients are first screened by safety laboratory
testing. Patients with diagnosed mild/general COVID-
19 infection are randomized to the following two
arms at a 1:1 ratio:
1. Arm 1 (control arm): lopinavir/ritonavir treatment
for diagnosed mild/general COVID-19 infection
uses lopinavir 800 mg/day and ritonavir 200 mg/day
for no more than 10 days
2. Arm 2 (investigation arm): chloroquine phosphate
treatment using chloroquine phosphate 1000 mg/
day, equivalent to chloroquine 600 mg/day for no
more than 10 days
The CRF is shown in Fig. 1. The schedule of treatment
visits and data collection (also known as the CRF) is
shown in Table 1.
Researchers will evaluate treatment adherence dur-
ing each visit. If a scheduled visit is delayed or can-
celled, the research team will contact the participant
at once. No treatment or intervention is prohibited
for any of the participants.
Page 3 of 9
Outcomes
The primary outcome is the clinical recovery time of no
more than 28 days after the completion of therapy and
follow-up. The secondary outcomes include the rate of
treatment success after the completion of therapy and
follow-up, the time of treatment success after no more
than 28 days, the rate of serious adverse events (SAEs)
during the completion of therapy and follow-up, and the
time to return to normal temperature (calculated from
the onset of illness) during the completion of therapy
and follow-up.
Definitions
The clinical recovery time and adverse events
We define the clinical recovery time as the time (in
hours, no more than 28 days) from the start of study
drug intervention to normalization of body temperature,
respiratory symptoms (cough, nasal stuffiness, nasal dis-
charge, etc.), respiratory frequency, and blood-oxygen
saturation. Specifically, also meeting the following cri-
teria at the same time:
① No fever: axillary body temperature ≤ 37.2 °C
② Relief of respiratory symptoms (72 consecutive hours)
③ Respiration rate ≤ 24/min (resting state)
Liu et al. Trials (2020) 21:622 Page 4 of 9

Table 1 The schedule of treatments and data collection

The SOFA (Sequential Organ Failure Assessment) score predicts mortality risk for patients in the intensive care unit based on laboratory results and clinical data1
Coagulation index: PT prothrombin time, APTT activated partial prothrombin time, Fib fibrinogen, D-Dimer D-dimer, PLT platelet count
Inflammatory factors: various cytokines involved in inflammation, such as interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, etc.
PCT (procalcitonin): a protein that increases when severe bacterial, fungal, and parasitic infections, sepsis, and multiple organ failure occur
− D0: before the research; D0: start of the research; D1: 1st day of the research; D2: 2nd day of the research; D3: 3rd day of the research; D4: 4th day of the
research; D5: 5th day of the research; D6: 6th day of the research; D7: 7th day of the research; D10: 10th day of the research; D14: 14th day of the research; D21:
21st day of the research; D28: 28th day of the research; D29: after the research
References:
1 Medlej K. Calculated decisions: sequential organ failure assessment (SOFA) score. Emerg Med Pract 2018;20:CD1-CD2.
Liu et al. Trials (2020) 21:622
④ Fingertip blood oxygen > 94%
Adverse events (AEs) refer to adverse medical events
that occur after a patient or clinical trial participant re-
ceives a drug, but they are not necessarily causally re-
lated to treatment.
Serious adverse events (SAEs) refer to events that re-
quire hospitalization, prolonged hospital stay, disability,
affect working ability, are life-threatening or fatal, cause
congenital malformation and other events that occur
during the clinical trial.
Treatment outcomes
We define treatment success as a patient whose throat-
swab SARS-CoV-2 real-time fluorescent reverse tran-
scription polymerase chain reaction (RT-PCR) nucleic
acid is positive at the beginning of the treatment but is
negative at least twice consecutively after the treatment
and remains negative.
Participants
Inclusion criteria
1. Age ≥ 18 years
2. Patients diagnosed with COVID-19 according to
the criteria of the seventh edition of the Treatment
Plan of China for new coronavirus pneumonia
(URL: http://202.116.81.74/cache/4/03/www.nhc.
gov.cn/5d9aa1423a8a577e1cc197a0d3c434d8/ce3e6
945832a438eaae415350a8ce964.pdf):
① Epidemiological history:
(a) Within 14 days before the onset of illness, a
history of travel or residence in Wuhan and
surrounding areas, or other communities with
reported cases
(b) Within 14 days before the onset of illness,
exposure to a person with COVID-19 infec-
tion (positive nucleic-acid test)
(c) Exposure to patients with fever or respiratory
symptoms from Wuhan and surrounding
areas, or communities with case reports
within 14 days before illness onset
(d) Aggregated disease: two or more cases of fever
or respiratory symptoms occurring in a small
area, such as home, office, school class, etc.,
within 2 weeks
② Clinical manifestations:
(a) Fever or respiratory-tract symptoms: cough,
nasal stuffiness, nasal discharge, etc.
(b) Normal or decreased white-blood-cell counts
in the early stages of disease; normal or de-
creased lymphocyte counts
(c) Multiple, small, patchy shadows and
interstitial changes in the early stages of chest
Page 5 of 9
imaging, which are evident in the
extrapulmonary zones, and which develop
multiple “ground-glass” infiltrations and
infiltrates throughout both lungs. In severe
cases, pulmonary consolidation may occur,
but the formation of pleural effusion is rare
③ Confirmed conditions: fulfillment of any one of
the epidemiological history items and any two of
the clinical manifestation items or three clinical
manifestation items if no epidemiological history
is available, in addition to meeting one of the
following etiological or serological criteria:
(a) Real-time fluorescent RT-PCR detects novel
coronavirus nucleic acid
(b) The gene-sequencing results of patients’ speci-
mens (blood, stool, etc.) are highly homolo-
gous to those of known novel coronaviruses
(c) Serum SARS-CoV-2-specific antibodies IgM
and IgG are positive, serum SARS-CoV-2-spe-
cific IgG antibodies change from negative to
positive or the quantity of IgG in the recovery
phase is at least four times higher than in the
acute phase (3–5 days after illness onset)
3. Mild or general patients:
(a) Mild: mild clinical symptoms (only manifested
as low-grade fever, minimal fatigue, etc.), and no
pneumonic manifestations on imaging
(b) General: with fever, dry cough and other
respiratory-tract symptoms, visible pneumonic
imaging)
4. Those who have not used antiviral drugs
Exclusion criteria
Any of the following factors will lead to exclusion:
1. Patients with a history of allergy to chloroquine
phosphate, lopinavir, or ritonavir
2. Patients with hematological diseases
3. Patients with end-stage liver or kidney diseases
4. Patients with arrhythmia and/or chronic heart
disease
5. Patients known to have retinal disease or hearing
loss
6. Patients known to have mental illness
7. Patients who must use digitalis because of an
original underlying disease
8. Pancreatitis
9. Hemophilia
10. Favism
11. Female patients during pregnancy
Randomization
Grouping is carried out using a centrally stratified, ran-
domized block method. Before the trial, a statistical
Liu et al. Trials (2020) 21:622
expert will use SAS software to set the number of cen-
ters at four, the block size will be four, the number of
blocks will be 28, using a 1: 1 ratio between the experi-
mental group and the control group, will generate 112
random numbers and corresponding grouping informa-
tion. According to the haphazard allocation table used in
advance, the statistical expert gives random numbers (1–
112) in ascending order. Each random number and
grouping information correspond to an envelope. The
envelope is sealed and given to the researchers respon-
sible for screening. Qualified subjects are selected, and
the envelopes are received in the order of enrollment.
After the envelopes are opened, the random-number
and grouping information is removed, so that the sub-
jects will be randomly assigned to the experimental
group or the control group, and the corresponding treat-
ment and observations performed. Each subject’s ran-
dom number is unique and remains the same
throughout the trial.
Sample size
The hypothesis of this study is that the use of chloro-
quine phosphate instead of lopinavir/ritonavir will in-
crease the rate of throat-swab SARS-CoV-2 nucleic-acid
negative conversion.
The main therapeutic index of this study is the clinical
recovery time (after no more than 28 days), which is
from the beginning of the study drug intervention treat-
ment to the normalization of body temperature, respira-
tory symptoms, respiratory rate, and blood-oxygen
saturation. In the later analysis, the log-rank method is
used to compare the differences in clinical recovery time
between the two groups of patients. The sample size of
this study is calculated based on the log-rank method by
using the log-rank test (Lakatos) (median survival time)
module in the PASS 11.0 statistical software (see Add-
itional file: Sample size report” for details).
Based on clinical experience [4, 18], the median clin-
ical recovery time of the patients in the control group is
expected to be 8 days, and the median clinical recovery
time of patients in the experimental group can be short-
ened to 4 days (corresponding hazard ratio (HR) = 2.0)
112 patients (56 in each group) will be required to detect
this difference with a significant level of α = 0.05 (both
sides) with 85% confidence interval.
The trial is planned to be enrolled for 90 days,
followed up for 28 days, and a final analysis is performed
after 78 clinical recovery events occur. It is estimated
that the drop-out rate of the experimental group and the
control group is 5%.
Statistical analysis
The results of this study for efficacy outcomes will be
analyzed based on both intention-to-treat (ITT) and
Page 6 of 9
per-protocol (PP) approaches with a primary consider-
ation for ITT results. A PP analysis will be performed
secondarily. A safety analysis will be performed based on
the safety group.
The ITT group will include participants who are ran-
domized after satisfying the eligibility criteria and receive
one study drug at least once and have post-dose evalu-
ation data. The PP group will include participants who
satisfy the following conditions among the ITT group:
(1) those who completed all planned visits and (2) those
who did not receive and use drugs or treatments that
may affect the evaluation of efficacy during the study.
The safety analysis group will include participants who
received study drugs at least once and have post-dose
safety evaluation data.
Efficacy outcomes
Comparisons will be performed using two-sided tests
with a statistical significance level of 5% unless stated
otherwise.
Analysis of primary outcomes
For the primary outcome of this trial, the clinical recov-
ery time of no more than 28 days after the completion of
therapy and follow-up will be estimated as the propor-
tion with a 95% confidence interval (CI) for each treat-
ment group. The difference between the control arm
and the experimental arm will subsequently be deter-
mined using the log-rank test. In order to control the in-
fluence of possible confounding factors such as gender
and age on the clinical recovery time, the Cox propor-
tional hazard model will be used to compare whether
the clinical recovery time of the two groups is different,
provide HRs and 95% CIs.
Analysis of secondary outcomes
The analysis of secondary outcomes will be described as
explorative outcomes. The rate of treatment success
after the completion of therapy and follow-up among
the two groups will be compared using the chi-square
test or Fisher’s exact test. The time of treatment success
after no more than 28 days, the time to normal
temperature (calculated from the onset of illness) during
the completion of therapy and follow-up will be calcu-
lated in each group and compared using the log-rank
test.
The rate of SAEs during the completion of therapy
and follow-up will be compared among the two groups
using the chi-square test or Fisher’s exact test.
Safety assessment
All AEs according to the Common Terminology Criteria
for Adverse Events (CTCAE) will be collected and docu-
mented, regardless of severity, seriousness, or relationship
Liu et al. Trials (2020) 21:622
to the study drug. We will summarize all AEs, include AE
frequency and percentage, and 95% CIs and compare the
occurrence rate of AEs in relationship to the study drug
and the severity of the two arms using the chi-square test
or Fisher’s exact test.
Stratified analysis
Primary and secondary outcomes will be analyzed separ-
ately in participants with throat-swab SARS-CoV-2 RT-
PCR-positive and throat-swab SARS-CoV-2 RT-PCR-
positive COVID-19 infection.
Data collection and management
Our study will use a paper version of the case report
form (CRF) and establish a clinical research database to
record all the information in the CRF. We will use the
software Epidata 3.1 for double data entry and proof-
reading of data, as well as manual verification and sys-
tem verification.
During the study, medical personnel not participating
in this study will monitor this trial. Monitors will visit
the database to monitor all aspects of the study includ-
ing adherence to the protocol and good clinical practice,
protection of participants, and data accuracy of the
study.
Supervision of the trial
The Office of the Clinical Research Center and the Med-
ical Ethics Committee of Sun Yat-sen University form
the Data and Safety Monitoring Board. Based on data re-
view during the trial conduct, the Board may provide
recommendations such as protocol amendment, con-
tinuation, or stopping of the trial. The datasets analyzed
during the current study are available from the corre-
sponding author on reasonable request.
Confidentiality
We will collect the participants’ personal information
only when necessary to evaluate efficacy, safety, and tol-
erability of the study drugs. Such information will be
collected and processed, taking precautions for compli-
ance with laws on privacy protection and the guarantee
of confidentiality. Paper files containing participants’
data (including personally identifiable information and
copies of signed consent forms) will be securely stored
in a locked office on sites in locked filing cabinets.
Digital files containing participants’ data will be stored
in password-protected files on university-maintained
servers. Access to study files will be restricted to autho-
rized personnel only.
The items in the present study protocol comply with
the Standard Protocol Items: Recommendations for
Interventional Trials (SPIRIT) Checklist (see the SPIRIT
Checklist and figure in Additional file).
Page 7 of 9
Clinical trial registration
The trial was registered under the registration number
ChiCTR2000029741 (http://www.chictr.org.cn/showproj.
aspx?proj=49263) on 11 February 2020. On 10 February,
2020, this research was approved by the Medical Ethics
Committee of the Fifth Affiliated Hospital of Sun Yat-
sen University, ZDWY[2020] Lunzi No. (K15–1).
Discussion
As of 10 April 2020, the total number of COVID-19 in-
fection diagnoses in the world was more than 1.3 mil-
lion, with more than 80,000 deaths (https://www.who.
int/dg/speeches/detail/the-cooperation-council-of-the-
turkic-speaking-states%2D%2D-10-april-2020). There is
no known curative treatment for COVID-19, neither
novel treatments nor vaccines. Cao’ study observed no
benefit with lopinavir/ritonavir treatment in severe
COVID-19 patients [19]. Lim’s study observed that the
beta-coronavirus viral load significantly decreased with
no or little coronavirus titers after administering lopina-
vir/ritonavir [2]. Gautret’s study [20] concluded that
chloroquine is significantly associated with viral-load re-
duction/disappearance in COVID-19 patients. In the
seventh edition of the Chinese version of the COVID-19
Diagnosis and Treatment Plan (http://www.nhc.gov.cn/
yzygj/s7653p/202003/46c9294a7dfe4cef80dc7f5912eb1
989/files/ce3e6945832a438eaae415350a8ce964.pdf), the
recommended antiviral drugs are lopinavir/ritonavir,
chloroquine phosphate and other drugs.
The Chinese have decreased the current epidemic situ-
ation in China by using the recommended drugs. The
relief of the epidemic in most provinces of China has at
least confirmed the effectiveness of the treatment to a
certain extent, but further strong and effective, evidence-
based data is needed.
The trial will be conducted in a clinical outpatient and
inpatient setting by experienced clinicians, and partici-
pants will be recruited from the patient base of the other
three hospitals participating in the trial. The purpose of
this prospective, open-label, multicenter randomized
controlled, comprehensive clinical study is to evaluate
the efficacy and safety of chloroquine phosphate and
lopinavir/ritonavir in patients with mild/general
COVID-19 infection. The results of this study should
provide meaningful information and evidence for clinical
practice and should help to design a proven and reason-
able RCT soon.
Limitations
Randomized controlled studies still have some design
limitations. First, the sample size we use is relatively
small and the 28-day treatment period is short. There-
fore, we will not be able to estimate possible relapses of
pneumonia after long-term treatment. Second, the
Liu et al. Trials (2020) 21:622
pathophysiology of novel coronavirus pneumonia has
not been elucidated. As only clinician assessment is used
(including lung computed tomography (CT) results and
count of viral load), there is no objective indicator to
judge the effect of treatment on COVID-19 infection. Fi-
nally, the follow-up period in this study was relatively
short. In light of these limitations, we will develop a
more reasonable treatment cycle and follow-up period
to explore the efficacy of chloroquine in patients with
COVID-19.
We also know that there will be many biases in the
open trial, and we have taken a number of measures to
control the possible bias in the trial, as follows:
(1) Strict exclusion criteria are formulated to effect-
ively control other confounding factors that may affect
the efficacy; (2) the trial uses random grouping to ensure
that the two groups of patients are comparable; (3) be-
fore the patient signs the informed consent form, the re-
searchers and the patients make full communication to
ensure that the patients understand the entire trial con-
tent, and try to eliminate the impact of the patient’s psy-
chological state on the trial effect; (4) the main and
secondary indicators for evaluating the efficacy are ob-
jective indicators to avoid the influence of subjective fac-
tors; (5) before the start of the trial, the researchers will
conduct unified system training to ensure the uniformity
and correctness of data collection and index evaluation.
Trial status
The trial was registered under the registration number
ChiCTR2000029741(http://www.chictr.org.cn/showproj.
aspx?proj=49263) on 11 February 2020. On 10 February
2020, this study was approved by the Medical Ethics
Committee of the Fifth Affiliated Hospital of Sun Yat-
sen University in Zhuhai, ZDWY[2020] Lunzi No. (K15–
1). Unique Protocol ID: ZDWY.GRBK.011. Protocol ver-
sion date: 7 February 2020. The first participant was ran-
domized in February 2020, and recruitment is ongoing.
It is estimated that the recruitment will be completed on
31 May 2020. The final results will be reported next
year.
Supplementary information
Supplementary information accompanies this paper at https://doi.org/10.
1186/s13063-020-04478-w.
Additional file 1.
Additional file 2. Standard Protocol Items: Recommendations for
Interventional Trials (SPIRIT) 2013 Checklist: recommended items to
address in a clinical trial protocol and related documents.
Abbreviations
ACE2: Angiotensin-converting enzyme 2; AE: Adverse event; COVID-
19: Corona Virus Disease-2019; CI: Confidence interval; CRF: Clinical research
flowchart; CTCAE: Common Terminology Criteria for Adverse Events;
HCoVs: Human corona viruses; HIV: Human immunodeficiency virus;
Page 8 of 9
ITT: Intention-to-treat; MAPK: Mitogen-activated protein kinase; PP: Per-
protocol; RT-PCR: Reverse transcription polymerase chain reaction; S
protein: Spike protein; SAE: Severe adverse event; SARS-CoV: Severe Acute
Respiratory Syndrome Corona Virus
Acknowledgements
Not applicable
Authors’ contributions
Professor JX carried out the design of the study. MH and ZH, carried out the
design of the study. XL, participated in the study design and drafted the
manuscript. HC and YS, participated in the study design and drafted the
manuscript. HZ and GC helped to draft the manuscript. YC, SL and YZ will
follow the research and help to collect data. All authors read and approved
the final manuscript.
Funding
This work was supported in part by National key Research and Development
(R&D plan "public security risk prevention and control and emergency
technical equipment": Novel coronavirus infection pneumonia diagnosis and
control key technology research (2020YFC082400), Guangdong Research and
Development (R&D) Program in Key Areas: Guangdong Scientific and
Technological Research Special fund for Prevention and Treatment of COVID-
19, Special fund for emergency research on SARS-CoV-2 from the
Guangzhou Regenerative Medicine and Health Guangdong Laboratory,
Cultivation Project of "Three Major Scientific Research Projects" of Sun Yat-
sen University in 2020, Emergency Project of New Coronavirus Prevention
and Control Science and Technology of Sun Yat-sen University.
Availability of data and materials
The datasets used or analyzed in the current study are available from the
corresponding author on reasonable request.
Ethics approval and consent to participate
This study was reviewed and approved by the Medical Ethics Committee of
the Fifth Affiliated Hospital of Sun Yat-sen University in Zhuhai on 10 Febru-
ary 2020, with file number ZDWY[2020] Lunzi No. (K15–1). This study is de-
signed in accordance with the principles of the Declaration of Helsinki. All
participants will provide written informed consent before enrollment.
Consent for publication
Not applicable
Competing interests
The authors declare that they have no competing interests.
Author details
1
Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen
University, Zhuhai, China. 2Department of Hospital Infection Control, The
Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China. 3Office of
Clinical Research Center, The Fifth Affiliated Hospital, Sun Yat-sen University,
Zhuhai, China.
Received: 29 February 2020 Accepted: 3 June 2020
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